What is the role of maintenance therapy in the treatment of acute promyelocytic leukemia (APL)?

Updated: May 03, 2019
  • Author: Sandy D Kotiah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

The role of maintenance therapy remains uncertain, especially for patients with low-risk APL who achieve molecular remission at the end of consolidation treatment. Most of the studies demonstrating benefit from maintenance therapy were conducted before the introduction of ATRA, ATO, or cytarabine for consolidation. [14]

The European APL group randomized patients to intermittent ATRA alone, ATRA plus 6-mercaptopurine (6-MP) and methotrexate, or observation. They found an improved overall survival in patients receiving ATRA or ATRA plus chemotherapy. Currently, the three-drug regimen of ATRA 45 mg/m2 daily given 15 days every 3 months, oral PO) 6-MP 60 mg/m2 once daily, and methotrexate 20 mg/m2 PO once weekly are administered for 2 years. Patients should be monitored for abnormal liver function and myelosuppression during this time period.

APL disease monitoring is usually done by reverse transcription polymerase chain reaction (RT-PCR) assay for the PML-RARA fusion transcript. [31] The RT-PCR assay can establish the diagnosis of APL when cytogenetics and fluorescence in situ hybridization (FISH) fail. The assay is useful for detecting minimal residual disease (MRD). The International Working Group recommends that the goal of treatment is complete molecular remission, which is evidenced by the absence of the fusion transcript using RT-PCR at a sensitivity threshold of 10-4.

Due to the lower sensitivity of the RT-PCR assay, the peripheral blood RT-PCR needs to be monitored every 3 months for the first 2 years. Then, the assay can be performed every 3-6 months for the next 3 years. The highest risk of relapse is in the first 2 years. Bone marrow samples may be more sensitive for detecting MRD, but peripheral blood samples are considered equivalent.

Avissati et al published the results of a 12-year follow-up for different maintenance regimens among patients who achieved a complete molecular remission (PML-RARA negative on RT-PCR) at the end of consolidation. In this study, 586 patients who were RT-PCR negative after consolidation were then randomized to four maintenance arms: (1) oral 6-MP and intramuscular methotrexate, (2) ATRA, (3) alternating oral 6-MP and intramuscular methotrexate with ATRA, or (4) observation alone. After 4 years, the chemotherapy alone arm was discontinued. [32]

The estimated 12-year disease-free survival was 68.9%; no difference in disease-free survival was found among all of the arms. This study raises the question of whether maintenance therapy should be done in patients who achieve a complete molecular remission at the end of consolidation. [32]


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